Other Glomerulonephritides
A number of diseases of diverse etiology display a nephritic syndrome as a major manifestation of their clinical presentation. The glomerular pathology is as varied as the clinical syndromes. Systemic vasculitides that also involve the glomeruli to cause a nephritic syndrome are discussed in the section on vascular disease and the kidney.
The hemolytic-uremic syndrome (HUS) chiefly affects children” under the age of 10 years and almost always follows a nonspecific gastrointestinal or influenzal syndrome. However, an adult form does occur and is seen primarily in women taking oral contraceptives or those in the postpartum period.
The acute phase of HUS is manifest by sudden onset of severe oligoanuria, hematuria, acute gastrointestinal symptoms, and gastrointestinal bleeding. Hypertension and volume overload are common, as are petechiae and ecchymoses. Oligoanuria and azotemia persist for one to two weeks in children, with spontaneous recovery the rule. Acute dialysis during this period has dramatically increased survival. Recurrence of the syndrome in children is well-documented, and these children may have progressive renal disease. The outcome in adults is much less favorable, with the vast majority of survivors requiring chronic dialysis or transplantation.
The striking feature of this syndrome is the microangiopathic hemolytic anemia, evidenced by fragmented circulating RBC’s accompanied by thrombocytopenia. Azotemia is universal and uremia is common. The glomeruli may show fibrin thrombi in capillary loops and segmental fibrinoid necrosis on light microscopy. Bilateral renal cortical necrosis occurs in the most severe cases, mostly in adults. A characteristic lesion is seen on electron microscopy in which capillary endothelial cells are separated from basement membranes by a space filled with finely granular basement membrane-like material.
Thrombotic thrombocytopenic purpura (TTP), which likely shares certain pathogenic origins with HUS, may also present with signs of nephritis and microangiopathic hemolytic anemia. In TTP, the clinical syndrome is dominated by neurological manifestations and the nephritis is evidenced by modest proteinuria, microhematuria, and modest degrees of azotemia. Glomerular pathology is similar to but less extensive than that of HUS.
Hereditary nephritis, or Alport’s syndrome, is a chronic GN that seems to follow X-linked inheritance. The clinical manifestations of renal disease are more common and more severe in males. The disease presents in childhood with recurrent bouts of gross hematuria, often with loin or vague abdominal pain. Sensorineural deafness is seen in about half the patients. Proteinuria is usually slight, and the nephrotic syndrome is uncommon. Males are especially prone to develop renal failure by age 20 to 30 years. Treatment does not alter the course of the disease, and it is not known to recur in transplanted kidneys.
Light microscopy findings are nonspecific, but an inflammatory interstitial component with foam cells becomes prominent as the disease progresses. There is no consistent immunofluores-cent finding in glomeruli, but electron microscopy shows a distinctive lesion. Widespread glomerular basement membrane alterations are evident, with severe GBM attenuation alternating with thick GBM’s split by a central lucent zone.
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